tbuckley/cabot-search huggingface dataset:
RANO 2.0: The revised Response Assessment in Neuro-Oncology (RANO) criteria for high- and low-grade glial tumors in adults designed for the future
Authors: Patrick Y Wen, Martin van den Bent, Michael A Vogelbaum, Susan M Chang
Journal: Neuro-Oncology (2023)

Journal Article Corrected proof RANO 2.0: The revised Response Assessment in Neuro-Oncology (RANO) criteria for high- and low-grade glial tumors in adults designed for the future Get access Patrick Y Wen, Patrick Y Wen Center For Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA Corresponding Author: Patrick Y. Wen, MD, Center For Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA (Patrick_wen@dfci.harvard.edu). https://orcid.org/0000-0002-0774-7700 Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin van den Bent, Martin van den Bent Department Neuro-Oncology, ErasmusMC Cancer Institute, Rotterdam, Netherlands Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael A Vogelbaum, Michael A Vogelbaum Departments of Neuro-Oncology and Neurosurgery, Moffit Cancer Center, Tampa, Florida, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan M Chang Susan M Chang Division of Neuro-Oncology, Department of Neurosurgery, University of California, San Francisco, California, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Neuro-Oncology, noad189, https://doi.org/10.1093/neuonc/noad189 Published: 29 September 2023 Article history Published: 29 September 2023 Corrected and typeset: 20 October 2023
Instant trachea reconstruction using 3D-bioprinted C-shape biomimetic trachea based on tissue-specific matrix hydrogels
Authors: Yuyan Sun, Yingying Huo, Xinyue Ran, Hongying Chen, Qingqing Pan, Yujie Chen, Ying Zhang, Wenjie Ren, Xiaoyun Wang, Guangdong Zhou, Yujie Hua
Journal: Bioactive Materials (2023)

Currently, 3D-bioprinting technique has emerged as a promising strategy to offer native-like tracheal substitutes for segmental trachea reconstruction. However, there has been very limited breakthrough in tracheal repair using 3D-bioprinted biomimetic trachea owing to the lack of ideal bioinks, the requirement for precise structural biomimicking, and the complexity of multi-step surgical procedures by mean of intramuscular pre-implantation. Herein, we propose a one-step surgical technique, namely direct end-to-end anastomosis using C-shape 3D-bioprinted biomimetic trachea, for segmental trachea defect repair. First, two types of tissue-specific matrix hydrogels were exploited to provide mechanical and biological microenvironment conducive to the specific growth ways of cartilage and fibrous tissue respectively. In contrast to our previous O-shape tracheal design, the tubular structure of alternating C-shape cartilage rings and connecting vascularized-fibrous-tissue rings was meticulously designed for rapid 3D-bioprinting of tracheal constructs with optimal printing paths and models. Furthermore, in vivo trachea regeneration in nude mice showed satisfactory mechanical adaptability and efficient physiological regeneration. Finally, in situ segmental trachea reconstruction by direct end-to-end anastomosis in rabbits was successfully achieved using 3D-bioprinted C-shape biomimetic trachea. This study demonstrates the potential of advanced 3D-bioprinting for instant and efficient repair of segmental trachea defects.
Evolutionary conservation of hippocampal mossy fiber synapse properties
Authors: Kenneth A. Pelkey, Geoffrey A. Vargish, Leonardo V. Pellegrini, Daniela Calvigioni, Julio Chapeton, Xiaoqing Yuan, Steven Hunt, Alex C. Cummins, Mark A.G. Eldridge, James Pickel, Ramesh Chittajallu, Bruno B. Averbeck, Katalin Tóth, Kareem Zaghloul, Chris J. McBain
Journal: Neuron (2023)
Molecular anatomy of adult mouse leptomeninges
Authors: Riikka Pietilä, Francesca Del Gaudio, Liqun He, Elisa Vázquez-Liébanas, Michael Vanlandewijck, Lars Muhl, Giuseppe Mocci, Katrine D. Bjørnholm, Caroline Lindblad, Alexander Fletcher-Sandersjöö, Mikael Svensson, Eric P. Thelin, Jianping Liu, A. Jantine van Voorden, Monica Torres, Salli Antila, Li Xin, Helena Karlström, Jon Storm-Mathisen, Linda Hildegard Bergersen, Aldo Moggio, Emil M. Hansson, Maria H. Ulvmar, Per Nilsson, Taija Mäkinen, Maarja Andaloussi Mäe, Kari Alitalo, Steven T. Proulx, Britta Engelhardt, Donald M. McDonald, Urban Lendahl, Johanna Andrae, Christer Betsholtz
Journal: Neuron (2023)

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.
Stress relief as a natural resilience mechanism against depression-like behaviors
Authors: Yiyan Dong, Yifei Li, Xinkuan Xiang, Zhuo-Cheng Xiao, Ji Hu, Yulong Li, Haohong Li, Hailan Hu
Journal: Neuron (2023)

Relief, the appetitive state after the termination of aversive stimuli, is evolutionarily conserved. Understanding the behavioral role of this well-conserved phenomenon and its underlying neurobiological mechanisms are open and important questions. Here, we discover that the magnitude of relief from physical stress strongly correlates with individual resilience to depression-like behaviors in chronic stressed mice. Notably, blocking stress relief causes vulnerability to depression-like behaviors, whereas natural rewards supplied shortly after stress promotes resilience. Stress relief is mediated by reward-related mesolimbic dopamine neurons, which show minute-long, persistent activation after stress termination. Circuitry-wise, activation or inhibition of circuits downstream of the ventral tegmental area during the transient relief period bi-directionally regulates depression resilience. These results reveal an evolutionary function of stress relief in depression resilience and identify the neural substrate mediating this effect. Importantly, our data suggest a behavioral strategy of augmenting positive valence of stress relief with natural rewards to prevent depression.
Deletion of the inhibitory co-receptor CTLA-4 enhances and invigorates chimeric antigen receptor T cells
Authors: Sangya Agarwal, M. Angela Aznar, Andrew J. Rech, Charly R. Good, Shunichiro Kuramitsu, Tong Da, Mercy Gohil, Linhui Chen, Seok-Jae Albert Hong, Pranali Ravikumar, Austin K. Rennels, January Salas-Mckee, Weimin Kong, Marco Ruella, Megan M. Davis, Gabriela Plesa, Joseph A. Fraietta, David L. Porter, Regina M. Young, Carl H. June
Journal: Immunity (2023)

Chimeric antigen receptor (CAR) T cell therapy targeting CD19 has achieved tremendous success treating B cell malignancies; however, some patients fail to respond due to poor autologous T cell fitness. To improve response rates, we investigated whether disruption of the co-inhibitory receptors CTLA4 or PD-1 could restore CART function. CRISPR-Cas9-mediated deletion of CTLA4 in preclinical models of leukemia and myeloma improved CAR T cell proliferation and anti-tumor efficacy. Importantly, this effect was specific to CTLA4 and not seen upon deletion of CTLA4 and/or PDCD1 in CAR T cells. Mechanistically, CTLA4 deficiency permitted unopposed CD28 signaling and maintenance of CAR expression on the T cell surface under conditions of high antigen load. In clinical studies, deletion of CTLA4 rescued the function of T cells from patients with leukemia that previously failed CAR T cell treatment. Thus, selective deletion of CTLA4 reinvigorates dysfunctional chronic lymphocytic leukemia (CLL) patient T cells, providing a strategy for increasing patient responses to CAR T cell therapy.
Antibodies targeting a quaternary site on SARS-CoV-2 spike glycoprotein prevent viral receptor engagement by conformational locking
Authors: Lihong Liu, Ryan G. Casner, Yicheng Guo, Qian Wang, Sho Iketani, Jasper Fuk-Woo. Chan, Jian Yu, Bernadeta Dadonaite, Manoj S. Nair, Hiroshi Mohri, Eswar R. Reddem, Shuofeng Yuan, Vincent Kwok-Man Poon, Chris Chung-Sing Chan, Kwok-Yung Yuen, Zizhang Sheng, Yaoxing Huang, Jesse D. Bloom, Lawrence Shapiro, David D. Ho
Journal: Immunity (2023)

SARS-CoV-2 continues to evolve, with many variants evading clinically authorized antibodies. To isolate monoclonal antibodies (mAbs) with broadly neutralizing capacities against the virus, we screened serum samples from convalescing COVID-19 patients. We isolated two mAbs, 12-16 and 12-19, which neutralized all SARS-CoV-2 variants tested, including the XBB subvariants, and prevented infection in hamsters challenged with Omicron BA.1 intranasally. Structurally, both antibodies targeted a conserved quaternary epitope located at the interface between the N-terminal domain and subdomain 1, uncovering a site of vulnerability on SARS-CoV-2 spike. These antibodies prevented viral receptor engagement by locking the receptor-binding domain (RBD) of spike in the down conformation, revealing a mechanism of virus neutralization for non-RBD antibodies. Deep mutational scanning showed that SARS-CoV-2 could mutate to escape 12-19, but such mutations are rarely found in circulating viruses. Antibodies 12-16 and 12-19 hold promise as prophylactic agents for immunocompromised persons who do not respond robustly to COVID-19 vaccines.
TDP-43 pathology is associated with increased tau burdens and seeding
Authors: Sandra O. Tomé, Grigoria Tsaka, Alicja Ronisz, Simona Ospitalieri, Klara Gawor, Luis Aragão Gomes, Markus Otto, Christine A. F. von Arnim, Philip Van Damme, Ludo Van Den Bosch, Estifanos Ghebremedhin, Celeste Laureyssen, Kristel Sleegers, Rik Vandenberghe, Frederic Rousseau, Joost Schymkowitz, Dietmar Rudolf Thal
Journal: Molecular Neurodegeneration (2023)

Most Alzheimer's Disease (AD) cases also exhibit limbic predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC), besides amyloid-β plaques and neurofibrillary tangles (NFTs) containing hyperphosphorylated tau (p-tau). LATE-NC is characterized by cytoplasmic aggregates positive for pathological TDP-43 and is associated with more severe clinical outcomes in AD, compared to AD cases lacking TDP-43 pathology TDP-43: AD(LATE-NC-). Accumulating evidence suggests that TDP-43 and p-tau interact and exhibit pathological synergy during AD pathogenesis. However, it is not yet fully understood how the presence of TDP-43 affects p-tau aggregation in symptomatic AD.In this study, we investigated the impact of TDP-43 proteinopathy on p-tau pathology with different approaches: histologically, in a human post-mortem cohort (n = 98), as well as functionally using a tau biosensor cell line and TDP-43A315T transgenic mice.We found that AD cases with comorbid LATE-NC, AD(LATE-NC+), have increased burdens of pretangles and/or NFTs as well as increased brain levels of p-tau199, compared to AD(LATE-NC-) cases and controls. The burden of TDP-43 pathology was also correlated with the Braak NFT stages. A tau biosensor cell line treated with sarkosyl-insoluble, brain-derived homogenates from AD(LATE-NC+) cases displayed exacerbated p-tau seeding, compared to control and AD(LATE-NC-)-treated cells. Consistently, TDP-43A315T mice injected with AD(LATE-NC+)-derived extracts also exhibited a more severe hippocampal seeding, compared to the remaining experimental groups, albeit no TDP-43 aggregation was observed.Our findings extend the current knowledge by supporting a functional synergy between TDP-43 and p-tau. We further demonstrate that TDP-43 pathology worsens p-tau aggregation in an indirect manner and increases its seeding potential, probably by increasing p-tau levels. This may ultimately contribute to tau-driven neurotoxicity and cell death. Because most AD cases present with comorbid LATE-NC, this study has an impact on the understanding of TDP-43 and tau pathogenesis in AD and LATE, which account for the majority of dementia cases worldwide. Moreover, it highlights the need for the development of a biomarker that detects TDP-43 during life, in order to properly stratify AD and LATE patients.
Experimental and mathematical approaches for drug delivery for the treatment of wet age-related macular degeneration
Authors: Eduardo A. Chacin Ruiz, Katelyn E. Swindle-Reilly, Ashlee N. Ford Versypt
Journal: Journal of Controlled Release (2023)

Several chronic eye diseases affect the posterior segment of the eye. Among them age-related macular degeneration can cause vision loss if left untreated and is one of the leading causes of visual impairment in the world. Most treatments are based on intravitreally injected therapeutics that inhibit the action of vascular endothelial growth factor. However, due to the need for monthly injections, this method is associated with poor patient compliance. To address this problem, numerous drug delivery systems (DDSs) have been developed. This review covers a selection of particulate systems, non-stimuli responsive hydrogels, implants, and composite systems that have been developed in the last few decades. Depending on the type of DDS, polymer material, and preparation method, different mechanical properties and drug release profiles can be achieved. Furthermore, DDS development can be optimized by implementing mathematical modeling of both drug release and pharmacokinetic aspects. Several existing mathematical models for diffusion-controlled, swelling-controlled, and erosion-controlled drug delivery from polymeric systems are summarized. Compartmental and physiologically based models for ocular drug transport and pharmacokinetics that have studied drug concentration profiles after intravitreal delivery or release from a DDS are also reviewed. The coupling of drug release models with ocular pharmacokinetic models can lead to obtaining much more efficient DDSs for the treatment of age-related macular degeneration and other diseases of the posterior segment of the eye.
A deep-learning pipeline to diagnose pediatric intussusception and assess severity during ultrasound scanning: a multicenter retrospective-prospective study
Authors: Yuanyuan Pei, Guijuan Wang, Haiwei Cao, Shuanglan Jiang, Dan Wang, Haiyu Wang, Hongying Wang, Hongkui Yu
Journal: npj Digital Medicine (2023)

Ileocolic intussusception is one of the common acute abdomens in children and is first diagnosed urgently using ultrasound. Manual diagnosis requires extensive experience and skill, and identifying surgical indications in assessing the disease severity is more challenging. We aimed to develop a real-time lesion visualization deep-learning pipeline to solve this problem. This multicenter retrospective-prospective study used 14,085 images in 8736 consecutive patients (median age, eight months) with ileocolic intussusception who underwent ultrasound at six hospitals to train, validate, and test the deep-learning pipeline. Subsequently, the algorithm was validated in an internal image test set and an external video dataset. Furthermore, the performances of junior, intermediate, senior, and junior sonographers with AI-assistance were prospectively compared in 242 volunteers using the DeLong test. This tool recognized 1,086 images with three ileocolic intussusception signs with an average of the area under the receiver operating characteristic curve (average-AUC) of 0.972. It diagnosed 184 patients with no intussusception, nonsurgical intussusception, and surgical intussusception in 184 ultrasound videos with an average-AUC of 0.956. In the prospective pilot study using 242 volunteers, junior sonographers' performances were significantly improved with AI-assistance (average-AUC: 0.966 vs. 0.857, P < 0.001; median scanning-time: 9.46 min vs. 3.66 min, P < 0.001), which were comparable to those of senior sonographers (average-AUC: 0.966 vs. 0.973, P = 0.600). Thus, here, we report that the deep-learning pipeline that guides lesions in real-time and is interpretable during ultrasound scanning could assist sonographers in improving the accuracy and efficiency of diagnosing intussusception and identifying surgical indications.
Selecting and describing control conditions in mobile health randomized controlled trials: a proposed typology
Authors: Simon B. Goldberg, Shufang Sun, Per Carlbring, John Torous
Journal: npj Digital Medicine (2023)

Abstract Hundreds of randomized controlled trials (RCTs) have tested the efficacy of mobile health (mHealth) tools for a wide range of mental and behavioral health outcomes. These RCTs have used a variety of control condition types which dramatically influence the scientific inferences that can be drawn from a given study. Unfortunately, nomenclature across mHealth RCTs is inconsistent and meta-analyses commonly combine control conditions that differ in potentially important ways. We propose a typology of control condition types in mHealth RCTs. We define 11 control condition types, discuss key dimensions on which they differ, provide a decision tree for selecting and identifying types, and describe the scientific inferences each comparison allows. We propose a five-tier comparison strength gradation along with four simplified categorization schemes. Lastly, we discuss unresolved definitional, ethical, and meta-analytic issues related to the categorization of control conditions in mHealth RCTs.
Shell Formulation in Soft Gelatin Capsules: Design and Characterization
Authors: Almudena Naharros‐Molinero, María Ángela Caballo‐González, F. Javier de la Mata, Sandra García‐Gallego
Journal: Advanced Healthcare Materials (2023)

Soft gelatin capsules (SGCs) are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients are dissolved, dispersed, or suspended in a liquid or semisolid fill, which is covered with a gelatin shell. Several factors can modify the properties of the gelatin shell and subsequently affect their operative handling during manufacturing process and the stability of the soft gelatin capsules. Three elements appear to be crucial: the shell formulation (type and content of the different components such as gelatins-source, extraction method-plasticizers, or additives); the manufacture and storage conditions (temperature, humidity, light) as well as the interactions between fill-shell formulas. Mechanical and thermal analysis arise as straightforward but highly useful tools to monitor the properties of the gelatin shell. This review provides an updated overview on the shell formulation and design. Additionally, it presents the uses of mechanical and thermal techniques to characterize and evaluate the impact of different parameters on the gelatin behavior over the production and stability of these pharmaceutical forms. This will help to detect changes that are yet not visible by visual inspection ensuring a suitable finished product over its shelf-life.
Personalization and localization as key expectations of digital health intervention in women pre- to post-pregnancy
Authors: V Vien Lee, Smrithi Vijayakumar, Wei Ying Ng, Ni Yin Lau, Qiao Ying Leong, Delicia Shu Qin Ooi, Lin Lin Su, Yung Seng Lee, Shiao-Yng Chan, Agata Blasiak, Dean Ho
Journal: npj Digital Medicine (2023)

Abstract Health behaviors before, during and after pregnancy can have lasting effects on maternal and infant health outcomes. Although digital health interventions (DHIs) have potential as a pertinent avenue to deliver mechanisms for a healthy behavior change, its success is reliant on addressing the user needs. Accordingly, the current study aimed to understand DHI needs and expectations of women before, during and after pregnancy to inform and optimize future DHI developments. Forty-four women (13 pre-, 16 during and 15 postpregnancy; age range = 21–40 years) completed a 60-minute, semistructured, qualitative interview exploring participant’s experience in their current phase, experience with digital health tools, and their needs and expectations of DHIs. Interviews were audio-recorded, transcribed verbatim and thematically analyzed. From the interviews, two core concepts emerged—personalization and localization of DHI. Between both concepts, five themes and nine subthemes were identified. Themes and subthemes within personalization cover ideas of two-way interactivity, journey organization based on phases and circumstances, and privacy trade-off. Themes and subthemes within localization cover ideas of access to local health-related resources and information, and connecting to local communities through anecdotal stories. Here we report, through understanding user needs and expectations, the key elements for the development and optimization of a successful DHI for women before, during and after pregnancy. To potentially empower downstream DHI implementation and adoption, these insights can serve as a foundation in the initial innovation process for DHI developers and be further built upon through a continued co-design process.
Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation
Authors: Shan Gao, Meng Liu, Dongzhu Liu, Xinru Kong, Yuelin Fang, Yingying Li, Hang Wu, Jianbo Ji, Xiaoye Yang, Guangxi Zhai
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Growing evidence suggests that the presence of cancer stem cells (CSCs) is a major challenge in current tumor treatments, especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis. Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy. In this work, we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid (ATRA) via biomineralization. This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters, which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration. With the help of CSC differentiation induced by ATRA, IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner. Furthermore, ATRA can boost immunogenic cell death induced by phototherapy, thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells. Taken together, this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation, improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.